PROJECT SUMMARY Depression is a leading contributor to the global burden of disease, and rates of depression increase rapidly during adolescence, particularly for girls. Affect-biased attention is a putative mechanism underlying adolescent depression that may also represent a target for intervention. To better inform experimental therapeutics, this proposal tests a mechanistic model of the visuocortical dynamics underlying the role of affect-biased attention in the development of depression using a risk-enriched sample of adolescent girls with no history of major depression at baseline (n = 90). The proposal will use steady-state visual evoked potentials (SSVEPs), derived from EEG, to provide a temporally-sensitive biological index of attention to competing visual stimuli at the level of neuronal populations in the visual cortex. The candidate proposes that increased stimulus-driven attention to distracting negative stimuli (assessed using SSVEPs as a novel visuocortical probe), which occurs at the expense of goal-directed attention to task-relevant stimuli, serves as a mechanistic precursor in the development of adolescent depression. The study will use a repeated-measures multi-wave assessment of depressive symptoms and SSVEP indices of affect-biased attention. A pilot experimental manipulation will test a novel real time SSVEP neurofeedback training to target affect-biased attention. We hypothesize that SSVEP indices of affect-biased attention will characterize depressive symptoms at baseline (Aim 1) and predict future depressive symptoms (Aim 2) and that real time SSVEP neurofeedback training will ameliorate affect-biased attention and buffer mood reactivity (Aim 3). In the proposed K23, the candidate will expand on her strong foundation in vulnerability models of depression by gaining additional training in: 1) developmental cognitive-affective neuroscience, 2) neurophysiology and advanced SSVEP analysis, 3) longitudinal data analysis, and 4) experimental therapeutics. The Department of Psychiatry at the University of Pittsburgh provides the optimal scientific training environment to meet these career development goals. The candidate's mentors (Drs. Price, Silk, and Salisbury) and consultants (Drs. Akcakaya, Iyengar, Ladouceur, Pine, and Young) are ideally suited to guide the candidate's training given their combined expertise in the neuroscience of youth depression, neurophysiology, longitudinal high risk designs, and experimental therapeutics (including expertise in neurofeedback concepts and methods). This proposal will inform the design of larger R series grants that will test, for example, if SSVEP indices of affect-biased attention predict the onset of youth internalizing disorders and if real time SSVEP neurofeedback training can be used in personalized intervention/prevention. The proposed K23 will prepare the candidate to investigate mechanisms of adolescent depression and position her with the requisite skills to target these mechanisms therapeutically. This program of research has the potential to advance the field by improving the identification of adolescents at high risk for depression and identifying mechanistic targets of intervention during key developmental windows. ! !